From adolescence to Alzheimer's: a neurodevelopmental lifespan model of cognitive vulnerability.

BACKGROUND: Cognitive impairment and Alzheimer's disease are significant health problems worldwide, and there is an emerging evidence that they may partly originate from neurodevelopmental processes established during early life, specifically in adolescence. OBJECTIVE: This review integrate developmental neuroscience with the results of the Adolescent Brain Cognitive Development (ABCD) Study to examine how early genetic, environmental, and neurodevelopmental factors may be relevant to the long-term trajectories of cognitive aging. RESULTS: There is an interplay between genetic vulnerability (APOE, CLU, BIN1, polygenic and epigenetic) and early brain and cognitive pathways in AD. These effects are modified by various environmental and lifestyle factors, including socioeconomic status, physical activity, diet, stress, and the use of substances. The neurodevelopmental processes of synaptic pruning, myelination, and network reorganization regulate vulnerable brain regions that are susceptible to AD, including the hippocampus and prefrontal cortex. The ABCD data demonstrate associations between adolescent environmental exposures and neurodevelopmental characteristics that may be relevant to lifelong brain health. However, their relationship with later AD remains hypothetical. CONCLUSION: The lifespan approach emphasizes that genetic, environmental, and developmental functions are interrelated in determining variations in cognitive aging. Identifying early life determinants may help generate hypotheses for future biomarkers and preventive strategies, although their predictive value for AD has not yet been established.